SQSTM1 (p62) is a multifunctional scaffolding protein that serves as a critical molecular adapter in selective autophagy processes 1. Its primary function involves bridging polyubiquitinated proteins and damaged organelles to autophagosomes for degradation through a process called aggrephagy 2. SQSTM1 operates through distinct molecular mechanisms: it first undergoes liquid-liquid phase separation upon binding ubiquitinated proteins via its UBA domain, forming cytoplasmic p62 bodies 2. Subsequently, it interacts with ATG8 family proteins (LC3A/B) on autophagosomes through its LIR motif, facilitating cargo recruitment and autophagic clearance 2. The protein is degraded along with its cargo during this process. SQSTM1 plays essential roles in mitophagy, where it mediates PINK1/Parkin-dependent clearance of damaged mitochondria by recruiting ubiquitinated VDAC1 to autophagosomes 3. Additionally, SQSTM1 phase separation can transform into P-bodies under stress conditions, which activate the NLRP3 inflammasome and induce inflammatory responses 4. Disease relevance includes associations with neurodegenerative disorders and inflammatory diseases. SQSTM1 dysfunction leads to accumulation of protein aggregates and impaired cellular homeostasis 56, making it a potential therapeutic target for autophagy-related pathologies.